Anti-N-Methyl-D-Aspartate (NMDA) Receptor Encephalitis Mimicking a Primary Psychiatric Disorder in an Adolescent.

Anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis likely has a wider clinical spectrum than previously recognized. This article reports a previously healthy 16-year-old girl who was diagnosed with anti-NMDA receptor encephalitis 3 months after onset of severe depression with psychotic features. She had no neurological manifestations, and cerebral magnetic resonance imaging (MRI) was normal. Slow background on electroencephalogram and an oligoclonal band in the cerebrospinal fluid prompted the search for anti-NMDA receptor antibodies. She markedly improved over time but remained with mild neuropsychological sequelae after a trial of late immunotherapy. Only a high index of suspicion enables recognition of the milder forms of the disease masquerading as primary psychiatric disorders.

Neo/adjuvant chemotherapy does not improve outcome in resected primary synovial sarcoma: a study of the French Sarcoma Group.

BACKGROUND: There are only scarce data about the benefit of adjunctive chemotherapy in patients with localized synovial sarcoma (SS). PATIENTS AND METHODS: Data from 237 SS patients recorded in the database of the French Sarcoma Group were retrospectively analyzed. The respective impact of radiotherapy, neo-adjuvant chemotherapy and adjuvant chemotherapy on overall survival (OS), local recurrence-free survival (LRFS) and distant recurrence-free survival (DRFS) were assessed after adjustment to prognostic factors. RESULTS: The median follow-up was 58 months (range 1-321). Adjuvant, neo-adjuvant chemotherapy and postoperative radiotherapy were administered in 112, 45 and 181 cases, respectively. In all, 59% of patients treated with chemotherapy received an ifosfamide-containing regimen. The 5-year OS, LRFS and DRFS rates were 64.0%, 70% and 57%, respectively. On multivariate analysis, age >35 years old, grade 3 and not-R0 margins were highly significant independent predictors of worse OS. After adjustment to prognostic factors, radiotherapy significantly improved LRFS but not DRFS or OS. Neither neo-adjuvant nor adjuvant chemotherapy had significant impact on OS, LRFS or DRFS. CONCLUSION: As for other high-grade soft-tissue sarcomas, well-planned wide surgical excision with adjuvant radiotherapy remains the cornerstone of treatment for SS. Neo-adjuvant or adjuvant chemotherapy should not be delivered outside a clinical trial setting.

Wound infection after excision and primary midline closure for pilonidal disease: risk factor analysis to improve patient selection.

BACKGROUND: Excision and primary midline closure for pilonidal disease (PD) is a simple procedure; however, it is frequently complicated by infection and prolonged healing. The aim of this study was to analyze risk factors for surgical site infection (SSI) in this context. METHODS: All consecutive patients undergoing excision and primary closure for PD from January 2002 through October 2008 were retrospectively assessed. The end points were SSI, as defined by the Center for Disease Control, and time to healing. Univariable and multivariable risk factor analyses were performed. RESULTS: One hundred thirty-one patients were included [97 men (74%), median age = 24 (range 15-66) years]. SSI occurred in 41 (31%) patients. Median time to healing was 20 days (range 12-76) in patients without SSI and 62 days (range 20-176) in patients with SSI (P < 0.0001). In univariable and multivariable analyses, smoking [OR = 2.6 (95% CI 1.02, 6.8), P = 0.046] and lack of antibiotic prophylaxis [OR = 5.6 (95% CI 2.5, 14.3), P = 0.001] were significant predictors for SSI. Adjusted for SSI, age over 25 was a significant predictor of prolonged healing. CONCLUSION: This study suggests that the rate of SSI after excision and primary closure of PD is higher in smokers and could be reduced by antibiotic prophylaxis. SSI significantly prolongs healing time, particularly in patients over 25 years.

Detection of micrometastases in sentinel lymph nodes from melanoma patients: direct comparison of multimarker molecular and immunopathological methods.

The technique of sentinel lymph node (SLN) dissection is a reliable predictor of metastatic disease in the lymphatic basin draining the primary melanoma. Reverse transcription-polymerase chain reaction (RT-PCR) is emerging as a highly sensitive technique to detect micrometastases in SLNs, but its specificity has been questioned. A prospective SLN study in melanoma patients was undertaken to compare in detail immunopathological versus molecular detection methods. Sentinel lymphadenectomy was performed on 57 patients, with a total of 71 SLNs analysed. SLNs were cut in slices, which were alternatively subjected to parallel multimarker analysis by microscopy (haematoxylin and eosin and immunohistochemistry for HMB-45, S100, tyrosinase and Melan-A/MART-1) and RT-PCR (for tyrosinase and Melan-A/MART-1). Metastases were detected by both methods in 23% of the SLNs (28% of the patients). The combined use of Melan-A/MART-1 and tyrosinase amplification increased the sensitivity of PCR detection of microscopically proven micrometastases. Of the 55 immunopathologically negative SLNs, 25 were found to be positive on RT-PCR. Notably, eight of these SLNs contained naevi, all of which were positive for tyrosinase and/or Melan-A/MART-1, as detected at both mRNA and protein level. The remaining 41% of the SLNs were negative on both immunohistochemistry and RT-PCR. Analysis of a series of adjacent non-SLNs by RT-PCR confirmed the concept of orderly progression of metastasis. Clinical follow-up showed disease recurrence in 12% of the RT-PCR-positive immunopathology-negative SLNs, indicating that even an extensive immunohistochemical analysis may underestimate the presence of micrometastases. However, molecular analyses, albeit more sensitive, need to be further improved in order to attain acceptable specificity before they can be applied diagnostically.

Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07.

BACKGROUND: We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). RESULTS: Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). CONCLUSIONS: The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.

Prognostic value of sentinel node biopsy in 327 prospective melanoma patients from a single institution

AIM: To confirm the accuracy of sentinel node biopsy (SNB) procedure and its morbidity, and to investigate predictive factors for SN status and prognostic factors for disease-free survival (DFS) and disease-specific survival (DSS). MATERIALS AND METHODS: Between October 1997 and December 2004, 327 consecutive patients in one centre with clinically node-negative primary skin melanoma underwent an SNB by the triple technique, i.e. lymphoscintigraphy, blue-dye and gamma-probe. Multivariate logistic regression analyses as well as the Kaplan-Meier were performed. RESULTS: Twenty-three percent of the patients had at least one metastatic SN, which was significantly associated with Breslow thickness (p<0.001). The success rate of SNB was 99.1% and its morbidity was 7.6%. With a median follow-up of 33 months, the 5-year DFS/DSS were 43%/49% for patients with positive SN and 83.5%/87.4% for patients with negative SN, respectively. The false-negative rate of SNB was 8.6% and sensitivity 91.4%. On multivariate analysis, DFS was significantly worsened by Breslow thickness (RR=5.6, p<0.001), positive SN (RR=5.0, p<0.001) and male sex (RR=2.9, p=0.001). The presence of a metastatic SN (RR=8.4, p<0.001), male sex (RR=6.1, p<0.001), Breslow thickness (RR=3.2, p=0.013) and ulceration (RR=2.6, p=0.015) were significantly associated with a poorer DSS. CONCLUSION: SNB is a reliable procedure with high sensitivity (91.4%) and low morbidity. Breslow thickness was the only statistically significant parameter predictive of SN status. DFS was worsened in decreasing order by Breslow thickness, metastatic SN and male gender. Similarly DSS was significantly worsened by a metastatic SN, male gender, Breslow thickness and ulceration. These data reinforce the SN status as a powerful staging procedure

Ataxia telangiectasia mutated (ATM) inhibition transforms human mammary gland epithelial cells.

Carriers of mutations in the cell cycle checkpoint protein kinase ataxia telangiectasia mutated (ATM), which represent 1-2% of the general population, have an increased risk of breast cancer. However, experimental evidence that ATM deficiency contributes to human breast carcinogenesis is lacking. We report here that in MCF-10A and MCF-12A cells, which are well established normal human mammary gland epithelial cell models, partial or almost complete stable ATM silencing or pharmacological inhibition resulted in cellular transformation, genomic instability, and formation of dysplastic lesions in NOD/SCID mice. These effects did not require the activity of exogenous DNA-damaging agents and were preceded by an unsuspected and striking increase in cell proliferation also observed in primary human mammary gland epithelial cells. Increased proliferation correlated with a dramatic, transient, and proteasome-dependent reduction of p21(WAF1/CIP1) and p27(KIP1) protein levels, whereas little or no effect was observed on p21(WAF1/CIP1) or p27(KIP1) mRNAs. p21(WAF1/CIP1) silencing also increased MCF-10A cell proliferation, thus identifying p21(WAF1/CIP1) down-regulation as a mediator of the proliferative effect of ATM inhibition. Our findings provide the first experimental evidence that ATM is a human breast tumor suppressor. In addition, they mirror the sensitivity of ATM tumor suppressor function and unveil a new mechanism by which ATM might prevent human breast tumorigenesis, namely a direct inhibitory effect on the basal proliferation of normal mammary epithelial cells.

Alcohol Brief Intervention in Primary Care: A Systematic Review

BACKGROUND: The purpose of the present review was to evaluate the evidence of the effectiveness of brief interventions aimed at reducing chronic alcohol use and harm related to alcohol consumption, conducted among individuals actively attending primary care but who were not seeking help for alcohol problems. METHODS: Randomised trials reporting at-least one outcome related to alcohol consumption and conducted in outpatients who were actively attending primary care centre or provider were selected using Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, ISI Web of Science, ETOH database, and bibliographies of the retrieved references and previous reviews. Selection and data abstraction were performed independently and in duplicate. We assessed validity of the studies and performed a meta-analysis for studies reporting alcohol consumption at 6 or 12 months follow up. RESULTS: We included 24 reports, reporting results of 19 trials and including 5,639 individuals. Seventeen trials reported a measure of alcohol consumption, eight reporting a significant effect of intervention. The meta-analysis showed a mean pooled difference of -41 (95% CI: −54; −28) g of pure ethanol per week in favour of brief intervention group. Evidences for other outcomes (laboratory values, health related quality of life, morbidity and mortality, health care utilisation) were inconclusive. CONCLUSION: Our systematic review indicated that brief intervention might be effective for both men and women in reducing alcohol consumption compared to a controlled intervention, in a primary health care population. The meta-analysis confirmed the reduction in alcohol consumption at 6 and 12 month. Further research should precise the components of effectiveness of brief intervention and the evidence of effects on morbidity, mortality, and quality of life related outcomes.

Prise en charge par le praticien des infections après transplantation d'organes solides [Management of infection after organ transplantation by the primary care physician]

The primary care physician is frequently consulted in first line for infectious complications in organ transplant recipients. Many infections without signs of severity can nowadays be managed on an outpatient basis. However, a number of clinical situations specific to transplant recipients may require special attention and knowledge. In particular, the general practitioner must be aware of the potential interactions between immunosuppressive and antimicrobial therapies, the risk of renal dysfunction as a consequence of diarrhea or urinary tract infection, and the diagnostic of CMV disease as a cause of fever without obvious source occurring several months after transplantation. Collaboration with the transplantation specialists is recommended in order to assure an optimal management of these patients.

Improving Students’ Learning Aspirations Beyond Post-Primary Education: A First Account of Two Non-Formal Education Programmes in Middle-Income

Non-formal education programmes are active in a number of developing countries. These programmes offer vulnerable students an opportunity to pursue their education although they were excluded for various reasons from the formal education systems. This paper examines the impact of two programmes (one in Mauritius, and one in Thailand) on their participants’ aspirations towards learning. We develop a methodology to measure the perception of students regarding their learning experience. More than a third of them, for example, believe that there is no barrier to their education. Most acknowledge the role of their teachers in raising their aspirations towards their educational achievement. When compared to male students, female students seem to value more the role of their education.

Intervention précoce dans les troubles psychotiques: quel rôle pour les praticiens de premier recours [Early intervention in psychotic disorders: which role for primary care practitioners?]

The development of early intervention in psychotic disorders has allowed a more optimistic approach and the development of more adapted and more efficient treatments. Primary care practitioners are often the first professional contact for patients developing psychosis, but diagnostic difficulties and patients' reluctance to engage in treatment are often an obstacle to private practice treatment. It is therefore important to provide more information to primary care practitioners on specific characteristics of these disorders and about locally available treatment structures in order to allow them to suspect this relatively rare diagnosis, facilitate the collaboration with flexible and accessible specialist services, that ideally should provide home treatment, and to improve prognosis.

ADOS: an educational primary prevention programme for preventing excess body weight in adolescents.

OBJECTIVE: The prevalence of adolescent obesity has increased considerably over the past decade in Switzerland and has become a serious public health problem in Europe. Prevention of obesity using various comprehensive programmes appears to be very promising, although we must admit that several interventions had generally disappointing results compared with the objectives and target initially fixed. Holistic programmes including nutritional education combined with promotion of physical activity and behaviour modification constitute the key factors in the prevention of childhood and adolescent obesity. The purpose of this programme was to incorporate nutrition/physical education as well as psychological aspects in selected secondary schools (9th grade, 14-17 years). METHODS: The educational strategy was based on the development of a series of 13 practical workshops covering wide areas such as physical inactivity, body composition, sugar, energy density, invisible lipids, how to read food labels, is meal duration important? Do you eat with pleasure or not? Do you eat because you are hungry? Emotional eating. For teachers continuing education, a basic highly illustrated guide was developed as a companion booklet to the workshops. These materials were first validated by biology, physical education, dietician and psychologist teachers as well as school medical officers. RESULTS: Teachers considered the practical educational materials innovative and useful, motivational and easy to understand. Up to now (early 2008), the programme has been implemented in 50 classes or more from schools originating from three areas in the French part of Switzerland. Based on the 1-week pedometer value assessed before and after the 1 school-year programme, an initial evaluation indicated that overall physical placidity was significantly decreased as evidenced by a significant rise in the number of steps per day. CONCLUSION: Future evaluation will provide more information on the effectiveness of the ADOS programme.

Changing Eating Habits - A Field Experiment in Primary Schools

We conduct a field experiment in 31 primary schools in England to test whether incentives to eat fruit and vegetables help children develop healthier habits. The intervention consists of rewarding children with stickers and little gifts for a period of four weeks for choosing a portion of fruit and vegetables at lunch. We compare the effects of two incentive schemes (competition and piece rate) on choices and consumption over the course of the intervention as well as once the incentives are removed and six months later. We find that the intervention had positive effects, but the effects vary substantially according to age and gender. However, we find little evidence of sustained long term effects, except for the children from poorer socio‐economic backgrounds.

Patient and physician gender concordance in preventive care in university primary care settings.

OBJECTIVE: To assess the quality of preventive care according to physician and patient gender in a country with universal health care coverage. METHODS: We assessed a retrospective cohort study of 1001 randomly selected patients aged 50-80years followed over 2years (2005-2006) in 4 Swiss university primary care settings (Basel, Geneva, Lausanne, Zürich). We used indicators derived from RAND's Quality Assessment Tools and examined percentages of recommended preventive care. Results were adjusted using hierarchical multivariate logistic regression models. RESULTS: 1001 patients (44% women) were followed by 189 physicians (52% women). Female patients received less preventive care than male patients (65.2% vs. 72.1%, p<0.001). Female physicians provided significantly more preventive care than male physicians (p=0.01) to both female (66.7% vs. 63.6%) and male patients (73.4% vs. 70.7%). After multivariate adjustment, differences according to physician (p=0.02) and patient gender (p<0.001) remained statistically significant. Female physicians provided more recommended cancer screening than male physicians (78.4 vs. 71.9%, p=0.01). CONCLUSIONS: In Swiss university primary care settings, female patients receive less preventive care than male patients, with female physicians providing more preventive care than male physicians. Greater attention should be paid to female patients in preventive care and to why female physicians tend to provide better preventive care.